Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in the plasma levels of components of the fibrinolytic system have been investigated in 80 patients suffering from gastrointestinal carcinomas. Urokinase antigen (RIA), tissue-type plasminogen activator antigen (ELISA) and plasminogen activator inhibitor (functional assay) were determined. Patients with pancreatic and colorectal carcinoma and metastases as well as those without metastases revealed significantly increased plasma urokinase levels. Those with gall bladder or gastric carcinoma did not show significantly elevated urokinase antigen levels compared to age-matched controls. Determination of tissue-type plasminogen activator antigen in all four carcinoma groups did not reveal significant differences when compared to an age-matched healthy control group. The concentrations of plasminogen activator inhibitor were significantly increased in all carcinoma groups; there being no differences between the patient groups with or without metastases. No correlations between the different parameters of the fibrinolytic system could be obtained.
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PMID:Pattern of fibrinolytic parameters in patients with gastrointestinal carcinomas. 310 63

We have studied the mechanism of a transforming growth factor-beta (TGF-beta)-stimulated production of type-1 plasminogen activator inhibitor (PAI-1) in WI-38 human lung fibroblasts. TGF-beta causes an early increase in the PAI-1 mRNA level which reaches a maximal 50-fold enhancement after 8 h. Blocking of protein synthesis with cycloheximide causes an equally strong increase in the level of PAI-1 mRNA. Quantitative studies of the effect of TGF-beta on PAI-1 protein levels in cell extracts and culture media by using monoclonal antibodies are consistent with the effect on PAI-1 mRNA. The results suggest a primary effect of TGF-beta on PAI-1 gene transcription, and also suggest the possibility that the transcription of this gene in non-induced cells may be suppressed by a short-lived negatively regulating protein. Urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators are decreased in the culture media of TGF-beta-treated cells concomitantly with the increase in PAI-1 accumulation. These findings show that a primary and important biological effect of TGF-beta may be an overall decreased extracellular proteolytic activity, and give an insight into the molecular mechanisms underlying TGF-beta action at the genetic level.
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PMID:Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts. 311 44

Plasminogen Activator Inhibitors (PA Inhibitor) have recently been identified in plasma. They are directed against t-PA and Urokinase. Two PA Inhibitors have been described: PA Inhibitor 1 from endothelial cells, hepatocytes and platelets and PA Inhibitor 2 from placenta. Enzymatic assays have been developed. They show that plasma levels of PA Inhibitor are very low under normal conditions, but a considerable increase (X10 or 20) is found in several pathological conditions (thrombo embolic disease, atherosclerosis, thrombotic risk factors (obesity, hypertriglyceridemia, diabetes) inflammatory syndrome, post operative period for PA Inhibitor 1, and in some physiological conditions (pregnancy for PA Inhibitor 2). These results plead for a pathogenic role of PA Inhibitor 1 in the development of thrombosis. Pharmacological products able to decrease the plasma level of PA Inhibitor are as yet scarce. Stanozolol, an anabolic steroid, some biguanides such as Metformin possess this property.
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PMID:[Anti-activator inhibitors of plasminogen]. 311 99

To determine if pulmonary perfusion was improved in acute pulmonary embolism after therapy with recombinant human tissue-type plasminogen activator (rt-PA), lung scans were obtained before and a mean of 22 hours after therapy in 19 patients. The posttherapy lung scans were compared with baseline, pretherapy scans with use of two semiquantitative methods--an anteroposterior view method, similar to that used in the Urokinase Pulmonary Embolism Trial, and a segmental method that emphasized pulmonary anatomy. There was an improvement in the defect score from 0.35 to 0.14 (P less than .01) when the anteroposterior view method was used and from 0.37 to 0.16 (P less than .01) when the segmental method was used. These encouraging results in the early posttherapy period suggest that rt-PA is especially effective in improving regional perfusion after pulmonary embolism and that a larger controlled trial of therapy with rt-PA for acute pulmonary embolism should be performed. Scoring lung scans with a segmental method is feasible and appropriate for present-day lung scan technique and should be considered in future studies.
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PMID:Pulmonary perfusion after rt-PA therapy for acute embolism: early improvement assessed with segmental perfusion scanning. 312 66

Urokinase- and tissue-type plasminogen activators (u-PA and t-PA) were identified immunohistochemically during reepithelialization of mouse and human skin wounds, by means of polyclonal and monoclonal antibodies. In incised mouse skin wounds u-PA immunoreactivity was found in keratinocytes at the edge of the wound after 12 h, and at days 2 to 10 after wounding it was found in virtually all keratinocytes of the epithelial outgrowth that gradually covered the wound. At day 14, the epidermis appeared normal and no u-PA immunoreactivity was detected. t-PA immunoreactivity was found from day 5 to day 10 in some keratinocytes located superficially in the epidermal outgrowths near the edge of the mouse wounds. In 3- and 5-day old human skin wounds, u-PA immunoreactivity was found in keratinocytes in the epithelial outgrowths, whereas no t-PA immunoreactivity was detected. No u-PA and no t-PA immunoreactivity was found in normal mouse and human epidermis. The specificity of the staining was supported by a variety of controls, including absorption of the polyclonal antibodies with highly purified u-PA and t-PA preparations and zymographic analysis of extracts of wound tissue. The function of the plasminogen activators during reepithelialization is discussed and it is suggested that the keratinocytes use plasmin activated by u-PA for dissecting their way through the provisional matrix in the upper part of the granulation tissue.
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PMID:Urokinase- and tissue-type plasminogen activators in keratinocytes during wound reepithelialization in vivo. 313 40

In this study, we examined the effects of various plasminogen activators on arachidonic acid release and prostacyclin biosynthesis in cultured rat aortic smooth muscle cells and bovine pulmonary artery endothelial cells. Prostacyclin was the major product formed from arachidonic acid in aortic smooth muscle cells and endothelial cells. When intact cells were incubated with streptokinase, one of the plasminogen activators, a significant stimulatory effect on prostacyclin biosynthetic activity in cells was evident without any cellular damage at all concentrations used (1-5,000 units/ml). Streptokinase also caused a marked release of arachidonic acid. However, when it was incubated with cell-free homogenates and [3H]arachidonic acid, it did not show any effects on prostacyclin biosynthesis. The addition of urokinase and tissue-type plasminogen activator had no effect on prostacyclin biosynthesis. Urokinase stimulated the release of arachidonic acid from cells, but it did not show any effect on prostacyclin release at any concentration of urokinase (1-5,000 units/ml). The release of arachidonic acid and the increased prostacyclin synthesis were not observed when tissue-type plasminogen activator was added. These results indicate that, among various plasminogen activators investigated, only streptokinase causes the release of arachidonic acid and prostacyclin. This could be a beneficial effect in thrombolytic therapy.
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PMID:Effect of various plasminogen activators on prostacyclin synthesis in cultured vascular cells. 314 95

Plasminogen activators were determined in intestinal tissue, obtained after surgery from patients with Crohn's disease and ulcerative colitis, and compared with normal intestinal tissue from colorectal cancer patients. The activity and quantity of tissue-plasminogen activator (t-PA) was found to decrease with the severity of inflammation in the patients with inflammatory bowel disease. Urokinase (u-PA) activity, however, was not changed compared with controls or in relation with severity of inflammation. In contrast, the level of u-PA antigen was found to be increased significantly in the inflammatory bowel disease tissues and was also related with severity of inflammation. The difference between u-PA activity and antigen in inflammatory bowel disease tissue could be attributed to an increase in inactive pro-u-PA and u-PA-inhibitor complexes. This increase in u-PA and the concomitant decrease in t-PA, are similar to those found in premalignant colonic adenomas, and might be related to the known increased cancer risk in inflammatory bowel disease.
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PMID:Plasminogen activators in the intestine of patients with inflammatory bowel disease. 314 42

Three cases of multicentric reticulohistiocytosis showing typical clinical, histologic, and ultrastructural findings are reported. In one, gastric cancer occurred; in the other two cases, severe polyarthritis was the only detectable internal involvement. The serine proteinases, urokinase and tissue-type plasminogen activator, were evaluated both with the autohistographic technique and spectrophotometric assay in lesional skin and synovia. Urokinase levels appeared grossly increased in the lesional synovia and moderately increased in the lesional skin. We suggest that urokinase, presumably released by the activated proliferating histiocytes, may play a major role in the extracellular matrix degradation leading to erosion of cartilage and adjacent bone in multicentric reticulohistiocytosis.
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PMID:Multicentric reticulohistiocytosis. Report of three cases with the evaluation of tissue proteinase activity. 314 26

In the past five years, the authors have performed stereotactic evacuation of hypertensive thalamic hematoma using Komai's CT-stereotactic apparatus in 44 cases. Liquefied hematoma was aspirated through a stereotactic cannula, and solid hematoma difficult to aspirate was dissolved by a plasminogen activator (Urokinase) and drained out through a silastic catheter. The mean ratio of the total volume of evacuated hematoma to the estimated volume by CT image was 83.8%. The recovery from motor paresis and consciousness disturbance was observed during the early postoperative days in most patients. Functional outcome (ADL) at 3 months after operation was as follows: 24 cases (54.5%) recovered to a full or partial (self-cared) social life, 15 (34.1%) required partial care at home and 2 (4.5%) remained bedridden. Although 3 patients died within 1 month after operation, the cause of death in these patients was admitted to have no direct relation to operative procedure or to rebleeding due to the Urokinase injection. Postoperative functional prognosis was not affected by the timing of the operation. The important factors affecting ADL were preoperative neurological grade and CT classification. This stereotactic method apparently exceeded the conventional craniotomy method in the functional outcome.
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PMID:[Stereotactic evacuation of hypertensive thalamic hematomas using plasminogen activator (urokinase)]. 351 66

Correlation between the deposition of alpha 2-plasmin inhibitor (alpha 2-PI), which is one of the inhibitory factors of fibrinolytic activities, in the glomeruli and the effects of urokinase therapy in patients with IgA nephropathy is described. Urokinase (UK) is a plasminogen activator derived from fresh human urine. Urinalysis and measurements of renal function tests, i.e., serum creatinine, blood urea nitrogen, glomerular filtration rate and phenolsulfonphtalein, were performed before and at 8 and 48 weeks after the administration of urokinase. There was marked improvement of proteinuria after UK therapy in patients without deposition of alpha 2-PI in the glomeruli. In contrast, the improvement of proteinuria after UK therapy was not observed in patients with positive deposition of alpha 2-PI in the glomeruli. It was concluded that the administration of UK may be useful for treatment of proteinuria in patients with IgA nephropathy.
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PMID:Significant correlation between the immunofluorescence of alpha 2-plasmin inhibitor in glomeruli and the effects of urokinase therapy in patients with IgA nephropathy. 353 Jan 7


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